Katharine Batt

Self-reported prevalence, description and management of pain in adults with haemophilia: Methods, demographics and results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study

Haemophilia is characterized by frequent haemarthrosis, leading to acute/chronic joint pain.

Successful treatment of intravenously abused oral Opana ER‐induced thrombotic microangiopathy without plasma exchange

In January 2013, the Centers for Disease Control and Prevention reported an illness associated with intravenous (IV) abuse of oral Opana ER (oxymorphone) in Tennessee. The clinical presentation of this syndrome was reported to resemble that of thrombotic thrombocytopenic purpura in the 15 patients reported; 12 were treated with plasma exchange. We report a similar case series of 15 patients with 18 episodes of thrombotic microangiopathy associated with recent IV abuse of oral Opana ER. In our series, we demonstrate that therapeutic plasma exchange is unnecessary; supportive care and treatment of underlying infections and renal dysfunction (without use of plasma exchange) resulted in clinical improvement in all patients. Thus, it appears that plasma exchange with associated costs and risks can be safely omitted in patients with thrombotic microangiopathy resulting from IV abuse of oral Opana ER. Am. J. Hematol. 89:695–697, 2014.

Supportive Management of Mucositis and Metabolic Derangements in Head and Neck Cancer Patients

Oral mucositis (OM) is among the most undesirable, painful, and expensive toxicities of cytotoxic cancer therapy, and is disheartening for patients and frustrating for caregivers. Accurate assessment of the incidence of OM has been elusive, but accumulating data suggests that reported OM frequency is significantly less than its actual occurrence. It has been suggested that over 90% of head and neck cancer (HNC) patients receiving radiotherapy (RT) with concurrent cisplatin experience severe OM with symptoms of extreme pain, mucosal ulceration and consequent limitations in swallowing and achieving adequate nutritional intake. This panoply of symptoms inevitably impacts a patients’ quality of life and their willingness to continue treatment. In spite of all the advances made in understanding the pathophysiology of OM, there is still no prophylactic therapy with proven efficacy. Strategies to limit the extent of OM and to manage its symptomatology include basic oral care, supportive medications, nutritional support and targeting aggressive treatments to high-risk patients. This review focuses on OM recognition, preventive measurements, and symptom-management strategies.

Internal consistency and item-total correlation of patient-reported outcome instruments and hemophilia joint health score v2.1 in US adult people with hemophilia: results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study

Background The Pain, Functional Impairment, and Quality of Life study was an observational, cross-sectional assessment of the impact of pain on functional impairment and quality of life in adult people with hemophilia (PWH) of any severity in the USA who experience joint pain and/or bleeding. Objective To assess internal consistency (IC) and item-total correlation (ITC) of assessment tools used in the Pain, Functional Impairment, and Quality of Life study. Methods Participants completed 5 patient-reported outcome instruments (EQ-5D-5L with visual analog scale, Brief Pain Inventory v2 Short Form [BPI], International Physical Activity Questionnaire [IPAQ], Short Form 36 Health Survey v2 [SF-36v2], and Hemophilia Activities List [HAL]) and underwent an optional physiotherapist-administered musculoskeletal exam (Hemophilia Joint Health Score v2.1) during routine visits. Reliability assessment included IC and ITC of each instrument. Results A total of 381 adult PWH (median age, 34 years) were enrolled. Participants were predominantly white/non-Hispanic (69.2%); 75% had congenital hemophilia A, and 70.5% had severe hemophilia. A total of 310 subjects reported bleeding within the past 6 months (mean [SD] number of bleeds, 7.1 [13.00]). IC was generally high across the instruments employed (Cronbach’s alpha 0.79–0.98) with the exception of HAL use of transportation (0.58) and IPAQ total physical activity (0.51). ITC was high (Pearson’s product-moment correlation coefficient >0.20) for all items except the “vigorous intensity activities” item of IPAQ, which was applicable to less than one-third of participants. The ITCs were generally highest in domains/scores that measured the functional consequences of hemophilic arthropathy on mobility and pain. Conclusion The demonstrated reliability (IC/ITC) of the patient-reported outcome instruments and Hemophilia Joint Health Score v2.1 support a role for these instruments in evaluating adult PWH in US clinical and research settings.

Construct validity of patient-reported outcome instruments in US adults with hemophilia: Results from the pain, functional impairment, and quality of life (P-FiQ) study

Background People with hemophilia (PWH) experience frequent joint bleeding, resulting in pain and functional impairment. Generic and disease-specific patient-reported outcome (PRO) instruments have been used in clinical studies, but rarely in the comprehensive hemophilia care setting. Objective The objective of this study was to assess construct validity of PRO instruments measuring pain, functional impairment, and health-related quality of life in US PWH with a history of joint pain/bleeding. Methods Adult male PWH completed 4 PRO instruments (EQ-5D-5L with visual analog scale, Brief Pain Inventory v2 Short Form [BPI], SF-36v2, Hemophilia Activities List [HAL]) and underwent a musculoskeletal examination (Hemophilia Joint Health Score v2.1 [HJHS]). Construct validity between index and domain scores was evaluated by Pearson product-moment correlation coefficient. Results A total of 381 PWH were enrolled. EQ-5D-5L Mobility correlated with BPI, SF-36v2, and HAL domains related to pain, physical function, and activity of the lower extremities. EQ-5D-5L Self-Care correlated only with HAL Self-Care. EQ-5D-5L Usual Activities correlated with BPI Pain Interference and domains within SF-36v2 and HAL related to pain and physical function/activities (particularly those involving the lower extremities). EQ-5D-5L Pain/Discomfort correlated with Bodily Pain and Physical Summary on SF-36v2, HAL Overall Activity, and all BPI pain domains. EQ-5D-5L Anxiety/Depression correlated with social/emotional/mental aspects of SF-36v2. On BPI, most pain domains correlated with Bodily Pain and Physical Health Summary on SF-36v2 and Overall Activity on HAL. On SF-36v2, Physical Functioning, Role Physical, Bodily Pain, and Physical Health summary scores correlated with all the domains of HAL except Self-Care. For HJHS, Ankle and Total scores correlated with SF-36v2 Physical Functioning and HAL Lying/Sitting, Leg Function, Complex Lower Extremity Activity, and Overall Activity. Conclusion All PRO instruments have high construct validity but provide different levels of detail in describing effects of hemophilia. Instrument choice may depend on individuals’ symptoms, treatment planning goals, or outcome tracking research objectives, with consideration for administrative burden.

Reliability of patient-reported outcome instruments in US adults with hemophilia: The Pain, Functional Impairment and Quality of life (P-FiQ) study

Background Hemophilia is marked by frequent joint bleeding, resulting in pain and functional impairment. Objective This study aimed to assess the reliability of five patient-reported outcome (PRO) instruments in people with hemophilia (PWH) in a non-bleeding state. Methods Adult male PWH of any severity and inhibitor status, with a history of joint pain or bleeding, completed a pain history and five PRO instruments (EQ-5D-5L, Brief Pain Inventory v2 [BPI], International Physical Activity Questionnaire [IPAQ], Short Form 36 Health Survey v2 [SF-36v2], and Hemophilia Activities List [HAL]) during their routine comprehensive care visit. Patients were approached to complete the PRO instruments again at the end of their visit while in a similar non-bleeding state. Concordance of individual questionnaire items and correlation between domain scores were assessed using intra-class correlation coefficient (ICC). Results Participants completing the retest (n=164) had a median age of 33.9 years. Median time for completion of the initial survey with PRO instruments was 36.0 minutes and for the five PRO instruments, median retest time was 21.0 minutes. The majority of participants had hemophilia A (74.4%), were white and non-Hispanic (72.6%), and self-reported arthritis/bone/joint problems (61%). Median/mean test-retest concordance was EQ-5D-5L 80.0%/79.1%, BPI 54.5%/58.9%, IPAQ 100%/100%, SF-36v2 77.8%/76.4%, and HAL 77.4%/75.9%. ICCs for test-retest reliability were EQ-5D-5L index 0.890; BPI – severity 0.950; BPI – interference 0.920; IPAQ total activity 0.940; SF-36v2 overall health 0.910; HAL total score 0.970. Conclusion All five PRO scales showed acceptable test-retest reliability in adult PWH. Therefore, the choice of instrument to be used for research or clinical care should be driven by instrument characteristics other than reliability.

Real‐world resource use and costs of haemophilia A‐related bleeding

Prophylaxis treatment is recommended for haemophilia patients, but associated real‐world economic costs and potential cost‐savings associated with improved disease management are not fully known. This study aimed to assess haemophilia A‐related resource use and cost by treatment type (prophylaxis versus non‐prophylaxis) and any associated cost‐savings.

Correlating S100B with disease course in a case of new onset, acquired thrombotic thrombocytopenic purpura (TTP): Could this be a new predictive biomarker in TTP?

Acute thrombotic thrombocytopenic purpura (TTP) is an aggressive thrombotic microangiopathy that if not treated, can have a 90% mortality rate. Clinical manifestations of this disease include profound thrombocytopenia, hemolytic anemia, and end‐organ dysfunction. Neurologic symptoms can occur in 80% of patients and range from mild confusion to coma (Scully et al., Br J Haematol 142:819‐826). Here, we present the clinical course of a patient diagnosed with new onset acquired TTP who presented with neurologic changes that waxed and waned during her disease course. In addition to usual clinical and laboratory markers for TTP severity and activity, we also collected and analyzed the protein S100B, an astroglial protein studied as a marker for central nervous system injury and impairment of the blood‐brain barrier. Our hypothesis here is that because TTP involves endovascular damage, S100B could function as a biomarker for neurologic dysfunction and ultimately, predict disease activity. As illustrated in this case, our patients S100B levels did appear to correlate with TTP disease activity and the trajectory of this protein seemed a better predictor of cognitive function. Furthermore, increased S100B velocity seemed to be the earliest indicator of a refractory TTP disease process requiring more intensive plasma exchange (TPE) therapy regimen. Therefore, we would suggest that S100B is a promising predictive biomarker of disease activity in guiding the intensity of TPE therapy for TTP as well as cognitive function.

What can we learn from using formal patient-reported outcome instruments to assess pain, functional impairment, anxiety, and depression in US adults with hemophilia?

People with hemophilia frequently suffer from arthropathy that leads to pain and functional impairment, ultimately resulting in reduced quality of life. The impact of pain and functional impairment on the lives of people with hemophilia was explored in the Pain, Functional Impairment, and Quality of Life (P‐FiQ) study. Various patient‐reported outcome (PRO) instruments were employed to assess the effect of pain and functional impairment on multiple aspects of health in people with hemophilia. The results presented in this supplement include detailed observations from PRO instruments regarding pain, functional impairment, anxiety, and depression, an analysis of the differences in health‐related quality of life across subgroups of patients defined by demographic and treatment‐related characteristics, and results of a modeling analysis to identify patient factors which influence perceptions of pain and functional impairment, independent of joint status. These data provide insights into how the results from PRO assessments may be used to evaluate outcomes for people with hemophilia in the clinical and research settings.

Assessments of pain, functional impairment, anxiety, and depression in US adults with hemophilia across patient-reported outcome instruments in the Pain, Functional Impairment, and Quality of Life (P-FiQ) study

Pain, functional impairment, anxiety, and depression associated with joint disease may affect health‐related quality of life (HRQoL) in people with hemophilia.